Data from: Diagnostic performance of alpha-fetoprotein, protein induced by vitamin K absence, osteopontin, Dickkopf-1 and its combinations for hepatocellular carcinoma

Background & Aims: Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance. Methods: Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers. Results: Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient’s age, etiology and tumor invasiveness of HCC affected the performance of each marker. Conclusions: AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.背景与目的：甲胎蛋白（Alpha-fetoprotein, AFP）是目前临床应用最广泛的肝细胞癌（hepatocellular carcinoma, HCC）血清生物标志物，尽管其存在一定局限性。维生素K缺乏诱导蛋白（protein induced by vitamin K absence, PIVKA-II）、骨桥蛋白（osteopontin, OPN）及Dickkopf-1（DKK-1）已被提出作为补充性生物标志物。本研究旨在对头对头比较AFP、PIVKA-II、OPN及DKK-1单独或联合使用时的诊断效能，以筛选最优的单一生物标志物或联合检测组合，并探究影响其诊断效能的临床相关因素。 方法：本研究纳入208例肝细胞癌患者与193例肝硬化对照患者的401份储存血浆样本，采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测血浆中AFP、PIVKA-II、OPN及DKK-1的水平，并针对每种单一生物标志物以及2~4种标志物的所有联合方案开展受试者工作特征曲线（receiver operating characteristic curve, ROC曲线）分析。 结果：四种生物标志物中，AFP的曲线下面积（area under the curve, AUC）最高，达0.786。各单一生物标志物对应的灵敏度与特异度分别为：AFP>20 ng/mL时为62%与90.2%；PIVKA-II>10 ng/mL时为51.0%与91.2%；OPN>100 ng/mL时为46.2%与80.3%；DKK-1>500 pg/mL时为50.0%与80.8%。在双标志物联合方案中，"AFP>20 ng/mL 或 DKK-1>500 pg/mL"的诊断效能最佳，灵敏度为78.4%，特异度为72.5%。三联或四联标志物联合并未进一步提升诊断效能。患者年龄、病因及肝细胞癌的肿瘤侵袭性会对各标志物的诊断效能产生影响。 结论：AFP是用于肝细胞癌诊断的最优单一生物标志物，联合检测AFP与DKK-1可最大化诊断收益。临床决策应综合考量影响各生物标志物诊断效能的多种因素。未来仍需持续探索新型肝细胞癌生物标志物。